title: Raltegravir pharmacokinetics in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C).
abstract: OBJECTIVE
  To describe raltegravir pharmacokinetics at steady-state in HIV/hepatitis C virus (HCV)-coinfected patients under antiretroviral (ARV) treatment with (n = 5) and without (n = 5) advanced liver cirrhosis (Child-Pugh C).
  
  
  METHODS
  This was a non-randomized, Phase I, parallel-assignment, open-label pharmacokinetic study in HIV/HCV-coinfected patients with Child-Pugh grade C hepatic cirrhosis. We recruited clinically stable HIV/HCV-coinfected adult patients with controlled HIV viraemia (<50 copies/mL) for at least 6 months. Raltegravir (400 mg twice daily) was added under fasting conditions for 5 days to the successful ritonavir-boosted protease inhibitor-based ARV regimen. The trial was registered in the ClinicalTrials.gov database (NCT01289951) (LIVERAL).
  
  
  RESULTS
  Raltegravir AUC0-12 and C12 were increased 1.72-fold (90% CI, 1.02 to 2.92) and 6.58-fold (90% CI, 2.92 to14.85), respectively, in patients with advanced liver cirrhosis. No safety issues were identified and raltegravir was well tolerated by all patients.
  
  
  CONCLUSIONS
  Raltegravir plasma levels are increased in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C). Despite the higher exposure, raltegravir was safe and well tolerated.
authors.affiliation: Infectious Diseases, Hospital Ramón y Cajal-IRYCIS, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Hernández-Novoa
authors.forename: Ana
authors.initials: A
authors.lastname: Moreno
authors.forename: María J
authors.initials: MJ
authors.lastname: Pérez-Elías
authors.forename: Carmen
authors.initials: C
authors.lastname: Quereda
authors.forename: Fernando
authors.initials: F
authors.lastname: Dronda
authors.forename: José L
authors.initials: JL
authors.lastname: Casado
authors.forename: Nadia
authors.initials: N
authors.lastname: Madrid-Elena
authors.forename: Mónica
authors.initials: M
authors.lastname: Aguilar
authors.forename: Emilio
authors.initials: E
authors.lastname: Fumero
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D019428:HIV Integrase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006526:Hepatitis C / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068898:Raltegravir Potassium
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium
keywords: end-stage liver disease; integrase inhibitors; plasma concentration